Organophosphate Pesticides Cause DNA Damage in Rats

by Kahea Kanuha

The growing use of pesticides in large-scale agricultural applications as well as for household purposes has resulted in their widespread distribution in the environment. To see if pesticide exposure damaged DNA, Ojha et al. (2011) evaluated the genotoxicity of chlorpyrifos (CPF), methyl parathion (MPT), and malathion (MLT), three organophosphate pesticides, when given individually or in combination to rats. The results showed that even a single dose of CPF, MPT, or MLT caused significantly high levels of DNA damage in all the rat tissues examined. DNA damage was also observed in microscopic examinations of tissue samples from the liver, brain, kidney, and spleen of rats exposed to one or more pesticides. It was also observed that the damaged DNA is repaired by the endogenous repair systems with time. When the pesticides are given together, they do not potentiate …

…the effects of each other. Organophosphate(OP) pesticides are a class of pesticide made of esters of phosphoric acid. Many of these pesticides irreversibly inactivate the acetylcholinesterase enzyme (AChE), which is essential to nerve function in insects, humans, and many other animals. AChE inhibition results in uncontrolled neuron firing, resulting in loss of respiratory control. In some cases, this results in death by asphyxiation. OP pesticides degrade much more rapidly than organochloride pesticides such as DDT, aldrin, and dieldrin, which often bioaccumulate since they remain in the environment for a longer time. However, OP pesticides generally have a greater acute toxicity, a measurement of the adverse effects of a substance resulting from a single exposure or multiple exposures in a short period of time.

To study the toxicity of OP pesticides, Ojha et al. measured DNA damage in the tissues of rats exposed to CPF, MPT, and MLT, singly or in combination. The pesticides were dissolved in corn oil and given to the rats orally in concentrations based on body weight. The more an animal weighed, the more pesticides given. Rats were killed 24, 48, and 72 hours after exposure. To determine the impact of chronic pesticide exposure, a second group of rats was given the median lethal dose of each pesticide for 60 days.

DNA damage was measured by electrophoresis, which separates DNA fragments based on their size and charge and results in the cell nuclei being visualized on a slide. DNA damage was quantified by the type of “comet” visualized on the slide: intact DNA appeared as round, condensed circles, while damaged DNA appeared as looser, fuzzier blobs. The looser and more scattered the comet, the more damaged the DNA. The results clearly showed that OP pesticide exposure, whether to single or multiple pesticides, caused significantly marked DNA damage in all of the rat tissues examined. There was between a 6.8- and 9.4-fold increase in DNA damage observed in all pesticide-exposed rats when compared to the control rats. Among the three pesticides tested, MPT showed the highest level of DNA damage in all the tissues examined.

When DNA damage was measured 48 and 72 hours after the pesticide treatment, the damage index was lower. This suggests that there is a time-dependent repair of the damage from pesticide exposure, although there were no further tests to see if the damaged DNA would be completely repaired with enough time. The differences in DNA damage among the organs could be explained by the fact that the DNA repair genes are expressed differently in various tissues.

In addition to measuring DNA damage through electrophoresis, Ojha et al. examined microscopic changes in tissue samples taken from the liver, brain, kidney, and spleen. Histological changes were seen in the tissues of all rats exposed to pesticides. The authors suggested that these changes might be a result of reactive oxygen species (ROS) causing damage to various membrane components of the cell. Cell structure damage due to ROS is known as oxidative stress and several investigations have examined the correlation between toxicant-induced oxidative stress and DNA damage.

Ojha, A., Yaduvanshi, S., Pant, S., Lomash, V., Srivastava, N. 2011. Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues. Wiley Periodicals, Inc. Environmental Toxicology 28, 543-552.  Paper here: http://bit.ly/X0m7sS

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